Cocaine Impact on Plasticity &Dendrite Morphology: Interaction with Environmental Complexity One of the most compelling examples of experience-dependent behavioral plasticity, whereby experience at one period in life changes behavior for a lifetime, is addiction. The propensity of addicts to relapse, even months to many years after the discontinuation of drug use,and long after withdrawal symptoms have subsided, provides stark evidence that drug use has long lasting consequences for behavior and psychological function. Similarly, very long-lasting changes in brain and behavior have been found in animal models, for example, following sensitization. Persistent experience-dependent changes in behavior and synaptic organization are presumably due to the effects of drugs and other experiences acting via coordinated actions on a variety of plasticity-related genes, and perhaps by influencing neurogenesis. Indeed, there is now considerable evidence that drugs of abuse usurp many of the same cellular and molecular mechanisms responsible for experience-dependent plasticity. This raises the hypothesis that changes in synaptic organization produced by experience may interact with those produced by exposure to drugs of abuse. The overall aim of this project is to explore the interaction between the effects of exposure to a drug of abuse, cocaine, and the effects of another life experience (living in a relatively complex environment), on the expression of key plasticity-related genes and on adult neurogenesis, in two genetically-distinct populations of rats that vary in their susceptibility to cocaine. Studies to date support the hypothesis that exposure to psychostimulant drugs may,under some circumstances and in some brain regions, saturate the potential for future plasticity (or produce "metaplasticity") and thus occlude the ability of subsequent experiences to induce molecules necessary for synaptic reorganization. The hypothesis that exposure to psychostimulant drugs may limit the potential for future plasticity in response to changes in environmental condition has important clinical implications. If true, it would suggest that the repeated use of some drugs of abuse might limit the ability to adapt positively to changes in environmental circumstances. Thus, some of the neuropsychological deficits seen in addicts could be due to limits on synaptic plasticity imposed by past druguse.